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February 2013, Supplement to Volume 17, Number
1
Article
Quality-of-Life Considerations With Taxane-Based Therapy in Metastatic Breast Cancer: A Case
Vignette
Cathy Maxwell, RN, OCN®
As with many other types of
chemotherapy, taxanes are associated with side
effects that can affect patients’ quality of life. One of the major side
effects of taxane therapy is taxane-induced
peripheral neuropathy (TIPN). The development of TIPN is accompanied by
troublesome burning, tingling, and numbness; TIPN also can affect patient
safety because of the decreased ability to perceive sensations (e.g., pain, heat).
Pain and fatigue are common side effects of taxane
therapy. These particular symptoms may hinder patients from working or
performing daily activities, thus affecting quality of life. This case vignette
provides an example of the symptoms that can accompany taxane
therapy, including TIPN. The case vignette also demonstrates the long-lasting
effects that TIPN can have on patients receiving taxane-based
therapy, as well as the hindrance to the ability to work and perform daily
activities because of numbness, pain, and fatigue. In addition, identification
and management of taxane-related side effects are
explored from the nursing perspective, and important aspects of patient
education are discussed.
The patient, a 78-year-old
woman, has a history of cholecystectomy, left knee replacement, hyperlipidemia,
and hypertension. She experienced menopause at age 53 and received only six
weeks of hormone-replacement therapy. The patient also has a family history of
cancer, including a sister who died of breast cancer and a maternal aunt who
died of ovarian cancer. At the time of her initial visit, the patient was
taking no medications. In January 2011, she experienced discomfort in her right
breast, for which she underwent a mammogram that revealed a mass that was further
confirmed by ultrasound and fine-needle aspirate. The patient also complained
of vague abdominal pains and had an elevated lactate dehydrogenase level (300
U/L). A positron-emission tomography/computed tomography scan revealed a liver
lesion. The primary tumor was observed to be 1.2 cm and was identified as
invasive ductal carcinoma that was positive for estrogen and progesterone
receptors and human epidermal growth factor receptor 2. The sentinel biopsy was
positive. The tumor was identified as T1c N2 M1. First-line chemotherapy with
paclitaxel plus trastuzumab was prescribed.
At the start of cycle 3, the
patient’s key concerns were fatigue, shortness of breath, diarrhea, aches and
pain, and alopecia. Her physical functioning was restricted in strenuous
activity, but she was able to perform light work. Prior to cycle 4, she
reported the same key symptoms as she did at her previous visit, as well as
mild bleeding and bruising problems and bilateral neuropathic symptoms such as
numbness, burning, or tingling in her hands. The patient’s physical functioning
also had decreased from an Eastern Cooperative Oncology Group performance
status (ECOG PS) of 0–1 (she was able to care for herself but was unable to
work, and she was able to be out of bed more than 50% of waking hours) (Oken et al., 1982). At the time of her fifth cycle, the
patient mentioned that she was experiencing numbness in her fingertips and
hands and that it was bothersome. She mentioned that, because of the numbness
in her fingers, she was now unable to cross-stitch, which was a hobby that she
truly enjoyed. She stated that she felt somewhat depressed because of this. At
the time, she also spoke of worsening fatigue as well as intermittent aches and
pains. At the sixth cycle, her physical functioning had declined to an ECOG PS
of 2 (unable to work and in bed more than 50% of waking hours). She continued
to express concern about fatigue, pain, diarrhea, and worsening numbness in her
fingertips and mentioned that she was now experiencing numbness in her toes and
feet. The patient had her seventh cycle of paclitaxel delayed because of
neutropenia, for which she received granulocyte–colony-stimulating factor
(G-CSF) therapy. The patient also had several subsequent cycles of paclitaxel
delayed because of continuing neuropathy. After the patient had received 12
cycles of paclitaxel, both she and the physician decided to stop paclitaxel
therapy because of the side effects. At her final cycle, in addition to the key
concerns from previous visits, the patient mentioned worsening of the
neuropathy in her fingers and hands, as well as difficulty when walking because
of the numbness in her feet. She said that the numbness in her hands now
prevented her from preparing her own food because she was afraid that she would
cut or burn herself; she also was unable to button her clothing and stated that
she was self-conscious about not being able to wear the clothing she normally
wears. She was offered medication (gabapentin) for the neuropathy, but refused
because she did not want to take another medication. Her ECOG PS was still 2,
which required her daughter to move in with her to provide care. The patient
said that she felt like she was a burden on her daughter.
The patient continued trastuzumab therapy. About one week after her last cycle of
paclitaxel, she reported dizziness and lightheadedness in addition to the
ongoing numbness, burning, or tingling, and her physical functioning was still
limited. She now stated that the neuropathy was affecting her feet to the
extent that she was worried about falling when she walked. She also mentioned
that she had dropped something twice because of the numbness in her hands. The
patient reported that she felt self-conscious about her hair loss and did not
want to exercise in the swimming pool because she did not want others to notice
that she had lost her hair. She continued to report no change in the
neuropathic symptoms at each visit. About four months after her last cycle of
paclitaxel, she reported continued numbness and tingling in her hands and feet
and that she was still unable to make her own food. At this point, she was
referred to a neurologist and was again offered medication (duloxetine) for the
neuropathy, which she refused because of the potential side effects. Her
physical functioning had improved to an ECOG PS of 1. Her daughter was able to
move out of the house and visited her 3–4 times per week now. About six months
after her last cycle of paclitaxel, the patient disclosed that she had fallen
during the time she was receiving paclitaxel, which resulted in a wrist injury.
She explained that she tripped going up the stairs because she was unable to
feel the step beneath her foot. She said that she did not want to mention her
fall earlier in fear that the physician would stop her treatment. In the
following months, the patient reported that the neuropathy began to slowly
improve; about one year after her last dose of paclitaxel, she said that the
neuropathy was still present but was “not as noticeable.” She was again able to
cook for herself and to button clothing; however, she stated that she was still
unable to cross-stitch. Figure 1 shows a timeline of
this patient’s experience with paclitaxel-induced neuropathy.
Taxanes have well-known safety profiles, and the symptoms
experienced by this patient, such as fatigue, diarrhea, alopecia, rash,
neutropenia, and neuropathy, are not uncommon for patients receiving paclitaxel
(Bristol-Myers Squibb, 2011). Unfortunately, many of these adverse events
affect patient quality of life. That was evident in the change in the patient’s
physical functioning score over time, as well as in her personal testimony at
each follow-up visit.
Neuropathy and Quality of Life
One of the most concerning
adverse effects of taxane therapy is neuropathy.
Although the exact mechanism behind taxane-induced
peripheral neuropathy (TIPN) is still unclear, the cause is likely from the
disruption of normal microtubule activity, which leads to impaired cell growth
(Scripture, Figg, & Sparreboom,
2006). Because microtubules are important for the development and maintenance
of neurons, this likely is the basis for the neurotoxicity induced by taxanes (Kobayashi & Mundel,
1998; Scripture et al., 2006). In addition, the solvent used to formulate
paclitaxel, Cremophor® EL (now renamed as Kolliphor® EL), has been associated with
neurotoxic effects in animal studies (Authier, Gillet, Fialip, Eschalier, & Coudore, 2000; Windebank, Blexrud, & de Groen, 1994). Unfortunately, effective therapies for
treating all patients with TIPN are not yet available (Wolf, Barton, Kottschade, Grothey, & Loprinzi, 2008). Several medications are used in the
treatment of neuropathic symptoms; however, the effectiveness of those
therapies is questionable (Pachman, Barton, Watson,
& Loprinzi, 2011). In addition, as evidenced by
the case vignette, many patients do not want to take neuropathy medications
because of the potential for side effects.
Gabapentin is commonly used
to treat neuropathic pain and is associated with dizziness, somnolence, edema,
and nausea (Pfizer Inc., 2012). Gabapentin is an antiepileptic drug, and many
of these types of agents have the potential to increase the risk of suicidal
thoughts or behavior in patients receiving them for any reason (Pfizer Inc.,
2012). Duloxetine, an antidepressant, also has been used to treat neuropathic
pain (Eli Lilly and Company, 2012). In a phase III study by Smith et al.
(2012), duloxetine was shown to be efficacious and well tolerated in patients who
had developed TIPN, with grade 2 fatigue being the most commonly reported
adverse event. Like gabapentin, duloxetine also is associated with nausea,
dizziness, somnolence, and an increased risk of suicidal thoughts and behaviors
(Eli Lilly and Company, 2012).
In addition to pharmacologic
interventions such as taxane dose reductions or
delays and topical, adjuvant, or opioid analgesics, nonpharmacologic
interventions for treating TIPN exist (i.e., exercise, hydrotherapy, massage,
acupuncture, electrotherapy, dietary supplements, and relaxation), and
healthcare providers commonly manage TIPN with dose reductions or dose delays
of the taxane. However, although these interventions
may be useful for treating TIPN, more research is needed to verify their
effectiveness.
Aside from the physical
symptoms of TIPN, such as numbness, burning, tingling, dizziness, and weakness,
TIPN affects patient quality of life in multiple ways (Almadrones,
McGuire, Walczak, Florio, & Tian,
2004; Bakitas, 2004). For many patients, neuropathic
symptoms contribute not only to discomfort but also emotional effects. Many
patients are emotionally affected by the inability to wear certain clothing
items or shoes (because of the inability to button or tie), put on makeup or
jewelry, perform a specific job, or participate in a hobby or sport (Tofthagen, 2010). For example, the case patient’s inability
to cross-stitch left her feeling somewhat depressed, and her inability to wear
the types of clothing she was used to made her feel
self-conscious. In addition, many patients become unable to care for themselves
and may need to rely on a caregiver, as the patient in the case vignette did
with her daughter (Anastasia & Hay, 2002). That reliance may cause patients
to feel like a burden to family members. Neuropathic symptoms also can
contribute to safety concerns. In the case vignette, after developing
paclitaxel-induced neuropathy, the patient spoke of bothersome numbness, became
afraid to cook for herself, had difficulty walking, and experienced a fall. In
addition, her physical functioning decreased over time during her treatment.
TIPN can persist well beyond the duration of treatment. Hershman
et al. (2011) reported that neuropathic symptoms were common for as many as two
years after adjuvant taxane therapy in survivors of
breast cancer. The patient in the case vignette experienced neuropathic
symptoms that lasted for more than one year after completion of paclitaxel
therapy.
Other Quality-of-Life Concerns
In addition to neuropathy,
many other side effects of taxane therapy can affect
patient quality of life. Neutropenia is a common side effect of all taxanes (Bristol-Myers Squibb, 2011; Celgene
Corporation, 2012; sanofi-aventis, 2010). Common
neutropenia-related symptoms include fatigue, negative emotional effects, and
fever (febrile neutropenia) (Friese, 2006). Because
neutrophils are involved in the immune response to infections, neutropenia can
predispose patients to infection (Bodey, 1986).
Fortunately, treatment with G-CSFs has demonstrated effectiveness in the
treatment of chemotherapy-induced neutropenia (Crawford et al., 1991; Green et
al., 2003). Another concerning side effect of taxanes
is fatigue, which can prevent patients from caring for themselves or
participating in many activities, including job responsibilities (Bakitas, 2004). Often, patients may be too tired to
exercise, which can lead to weight gain (Bakitas,
2004). Alopecia is another common side effect of taxane
therapy. The high visibility of this side effect can be emotionally difficult
for patients (Boehmke & Dickerson, 2005). Hair loss can severely affect
patient self-esteem and prevent the patient from participating in normal
activities. As mentioned in the case vignette, the patient reported that she
did not want to go into the swimming pool because she did not want others to
notice her hair loss. In addition, the patient
experienced a fall related to her neuropathic symptoms but did not mention this
fall to her physician until several months later. Patients may be afraid of
mentioning any taxane-related side effects to a
healthcare provider because they fear that the provider may decrease or delay
their dose of chemotherapy or that they will have to receive yet another
medication (with its own side-effect profile) (Reyes-Gibby,
McCrory, & Cleeland,
2003; Markman, 2006; Polomano
& Farrar, 2006). That, in turn, affects the patient’s quality of life
because of the feeling of having to just “put up with” side effects of taxane therapy.
Nursing Considerations
With regard to TIPN, proper
assessment is very important. Infusion nurses are a patient’s first line of
defense prior to receiving their infusion. If a nurse notices signs and
symptoms of TIPN, he or she can relay that information to the provider,
advanced practice nurse, or physician’s assistant. That information will help
the provider, advanced practice nurse, or physician’s assistant decide on a
plan of action, such as delaying or reducing the dose. Neurologic assessments
should be performed by healthcare providers at each visit (Tofthagen,
2010; Wickham, 2007). Unfortunately, many nurses do not have the time to
perform a thorough neurologic examination. To this end, education on methods
for early assessment of TIPN will help to improve the overall care of the
patient (Donovan, 2009). Although time often is limited, patient discussions
can take place anywhere, from the examination room to the hallway, and even
during walks to and from the infusion location. Some tips for quickly assessing
a patient for TIPN are listed in Figure 2. It
also is critical for the nurse to be able to distinguish the development of
TIPN from neuropathy related to other causes. Peripheral neuropathy is
generally bilateral and presents as “stocking-glove” dysesthesia,
which normally starts in the fingers and toes and moves upward (Donovan, 2009).
Other causes of peripheral neuropathy, such as tumor compression or blood
clots, do not normally display this pattern. On the other hand, neuropathy
caused by diabetes may present similarly to that caused by chemotherapy;
therefore, an awareness of a patient’s comorbid conditions is important in
assessing TIPN (Wolf et al., 2008).
Because patient education is
critical, nurses should discuss the potential for neuropathy with patients at
the initial visit (Barharmand, 2004). It also may be
helpful to remind patients of the potential for neuropathy at each visit to
help the patient understand why he or she is undergoing a neurologic
assessment. During discussions, healthcare providers should take care to not
frighten patients and to obtain feedback on their level of understanding of
what was discussed (Harris, 1998). Patients also should be made aware of the
potential safety hazards of developing neuropathy, such as falls and burns (Almadrones & Arcot, 1999;
Armstrong, Almadrones, & Gilbert, 2005; Paice, 2007). In addition, the caregiver should be involved
in as much of the patient education as possible (Harris, 1998). Caregivers
should be educated about patient safety by explanations of how they can help
the patient who is experiencing neuropathy (e.g., removing throw rugs from the
patient’s living areas, placing nonskid coverings on floors and stairs, keeping
rooms well lit) (Almadrones & Arcot,
1999; Paice, 2007). Some suggested interventions for
both patients and caregivers for preventing injuries from neuropathy can be
found in Figure 3.
Patients should be instructed
on the importance of reporting neuropathic symptoms as soon as possible (Markman, 2006). Many patients may not report TIPN symptoms
when they first begin to notice them or may underreport the extent of the TIPN
symptoms because they fear that their dose will be altered (Markman,
2006). Patients should be reassured that dose delays or reductions are a normal
part of managing neuropathy (Bristol-Myers Squibb, 2011; Celgene
Corporation, 2012; sanofi-aventis, 2010). In addition
to symptoms such as numbness, tingling, burning, and weakness, the patient should
be asked specifically about his or her ability to perform daily activities such
as walking, picking things up, and buttoning clothing (Bakitas,
2004; Visovsky, Collins, Abbott, Aschenbrenner,
& Hart, 2007). Often, when triggered, patients will be forthcoming with
information that they may not have otherwise remembered to discuss (Armstrong
et al., 2005). The patient also can be asked to demonstrate buttoning and
unbuttoning of clothing in the clinic, which is a good way of obtaining
information through observation. Although patient self-reports of neuropathic
symptoms may not always be accurate or complete, triggers such as the questions
in Figure 2 may help convey information about the side effects
they are experiencing.
Many of the mentioned nursing
considerations can be applied across a range of anticipated side effects.
Nurses need to educate themselves, patients, and caregivers on the potential
side effects of taxane therapy. It also is important
for patients to be assessed at each visit. In addition, a patient may be
reluctant to talk about symptoms he or she is experiencing for many reasons,
such as fear of dose reduction or delay, embarrassment, and the possible
addition of a new medication (Markman, 2006). Nurses
often can visually assess a change in gait; breathing difficulties; changes in
clothing, hairstyle, or makeup; or painful expression, and, from there, prompt
the patient to elaborate on any problems that he or she may be experiencing
(Armstrong et al., 2005; Bakitas, 2004). Nurses
should try to develop a relationship with patients and to help them understand
that they are there to help patients through their treatment. Patient education
is critical, and information should be provided through multiple avenues (e.g.,
video, written materials, verbal information) (Szpiro,
Harrison, Van Den Kerkhof, & Lougheed,
2008). Some patient education resources are provided in Figure 4. Providing information in “chunked” intervals (i.e.,
information spread out over the course of several visits) also can be helpful
(American Medical Association, 2007). Often, patients are anxious or may have
cognitive dysfunction, not to mention that dealing with a diagnosis of breast
cancer can be overwhelming; therefore, providing information in multiple ways
may help patients to better understand and retain it (Szpiro
et al., 2008). In addition, educating caregivers is a valuable way of ensuring
that information and instructions are available to patients when they are away
from the clinic.
Conclusion
Taxane-related symptoms can affect patient quality of life
both physically and emotionally. Each taxane has its
own unique safety profile that must be considered on an individual patient
basis. For example, all of the taxanes are associated
with the potential to develop peripheral neuropathy; however, compared with
paclitaxel and docetaxel, nab-paclitaxel has
demonstrated a faster time to improvement in peripheral neuropathy in two
clinical trials of patients with metastatic breast cancer (Gradishar
et al., 2005, 2012). As frontline managers of supportive care, nurses must
educate themselves on the identification and management of these symptoms to
help improve patient quality of life. Nurses taking the time to educate
themselves on the side-effect profile of the taxanes,
as well as the techniques for assessing the presence or severity of symptoms
such as TIPN, will ultimately ensure that patients receive the best care. In
addition, establishing and maintaining trust will facilitate open communication
between patients and nurses, which will play a major role in improving quality
of care.
Implications for Practice
Ø Taxane-induced peripheral
neuropathy can persist for an extended period of time, even after taxane therapy treatment is discontinued.
Ø Learning to identify and
manage patients with peripheral neuropathy is an important aspect of care.
Ø Educating the patient and
caregivers on the symptoms and dangers related to taxane-induced
peripheral neuropathy is a key role of oncology nurses.
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Cathy Maxwell, RN, OCN®, is the director of
Clinical Operations at Advanced Medical Specialties in Miami, FL. The author
received editorial support from Christopher Carter, PhD, of MediTech
Media, which was funded by Celgene Corporation. The
author is fully responsible for the content of and editorial decisions about
this article and received no honorarium for its development. Celgene Corporation provided funding for the publication of
this article and provided a medical accuracy review of content for author
consideration. The content of this article has been reviewed by independent
peer reviewers to ensure that it is balanced, objective, and free from
commercial bias. No financial relationships relevant to the content of this
article have been disclosed by the independent peer reviewers or editorial
staff. Mention of specific products and opinions related to those products do
not indicate or imply endorsement by the Clinical Journal of Oncology Nursing
or the Oncology Nursing Society. Maxwell can be reached at cmaxwellfla@gmail.com, with copy
to editor at CJONEditor@ons.org. (First submission October 2012. Revision submitted November
2012. Accepted for publication November 16, 2012.)
http://dx.doi.org/10.1188/13.CJON.S1.35-40